Type I interferons (IFN) are a class of natural cytokines that
includes a family of greater than 25 IFN[alpha]'s as well as
IFN-ß, and IFN-[omega]. Characterization of type 1 IFN's
demonstrates many differences in the primary sequence of these
molecules, implying an evolutionary divergence in biological
activity. Although type 1 IFN's have shown success in the treatment
of chronic HCV infection, most clinical use of type interferon has
been limited to the alpha 2 subtype. The mechanism of action of
type 1 IFN in the treatment of chronic HCV infection has yet to be
elucidated but may involve the antiviral, antiproliferative,
immunomodulatory, and cytokine/gene regulation activities of these
pleotropic molecules. In order to assess the potential for clinical
differences in the treatment of chronic HCV infection between IFN
[alpha] 2 and CIFN, a novel non-naturally occurring type 1 IFN, we
examined the in vitro antiviral, antiproliferative, NK cell
activation activity, cytokine induction and interferon stimulated
gene-induction activity of these two different IFN's. For all
comparisons, when compared on a equal mass basis, CIFN displayed
between five and one hundred times higher activity. In order to
elucidate the potential mechanism for the higher activity of CIFN
compared to IFN [alpha] 2, we studied the receptor binding
characteristics of the two IFN's by Scatchard analysis. The results
of the Scatchard analysis demonstrated a 10-fold higher binding
affinity for the IFN type 1 receptor for CIFN compared to
IFN-[alpha] 2. These unique biological properties of CIFN may lead
to a favorable clinical benefit in the treatment of chronic HCV
infection for CIFN when compared to the IFN [alpha] 2 due to the
increased biologic effects and higher receptor affinity of this new
molecule.
This research was funded by Amgen Inc., Boulder, CO.

Source: American Association for the Study of Liver Diseases
- 1996 Annual Meeting